The complement cascade is an important arm of the immune system that plays a key role in protecting the central nervous system (CNS) from infection. Recently, it has also become clear that complement proteins have fundamental roles in the developing and aging CNS that are distinct from their roles in immunity. During neurodevelopment, complement signalling is involved in diverse processes including neural tube closure, neural progenitor proliferation and differentiation, neuronal migration, and synaptic pruning. In acute neurotrauma and ischamic brain injury, complement drives inflammation and neuronal death, but also neuroprotection and regeneration. In diseases of the aging CNS including dementias and motor neuron disease, chronic complement activation is associated with glial activation, and synapse and neuron loss. Proper regulation of complement is thus essential to allow for an appropriately developed CNS and prevention of excessive damage following neurotrauma or during neurodegeneration. This review provides a comprehensive overview of the evidence for functional roles of complement in brain formation, and its dysregulation during acute and chronic disease. We also provide working models for how complement can lead to neurodevelopmental disorders such as schizophrenia and autism, and either protect, or propagate neurodegenerative diseases including Alzheimer’s disease and amyotrophic lateral sclerosis.

补体级联反应是免疫系统的重要组成部分，在保护中枢神经系统（CNS）免受感染中起关键作用。最近，也已经变得清楚的是，补体蛋白在发育和衰老的中枢神经系统中具有基本作用，与它们在免疫中的作用不同。在神经发育过程中，补体信号传导涉及多种过程，包括神经管闭合，神经祖细胞增殖和分化，神经元迁移和突触修剪。在急性神经外伤和缺血性脑损伤中，补体会驱动炎症和神经元死亡，还会导致神经保护和再生。在衰老的中枢神经系统疾病中，包括痴呆症和运动神经元疾病，慢性补体激活与神经胶质激活，突触和神经元丢失有关。因此，对补体的适当调节对于允许适当发展的中枢神经系统和预防神经外伤后或神经退行性病变期间的过度损害至关重要。这篇综述提供了关于补体在脑形成中的功能作用及其在急性和慢性疾病中失调的证据的全面综述。我们还提供补体如何导致神经发育障碍（例如精神分裂症和自闭症）以及保护或传播神经退行性疾病（包括阿尔茨海默氏病和肌萎缩性侧索硬化症）的工作模型。这篇综述提供了关于补体在脑形成中的功能作用及其在急性和慢性疾病中失调的证据的全面综述。我们还提供补体如何导致神经发育障碍（例如精神分裂症和自闭症）以及保护或传播神经退行性疾病（包括阿尔茨海默氏病和肌萎缩性侧索硬化症）的工作模型。这篇综述提供了关于补体在脑形成中的功能作用及其在急性和慢性疾病中失调的证据的全面综述。我们还提供补体如何导致神经发育障碍（例如精神分裂症和自闭症）以及保护或传播神经退行性疾病（包括阿尔茨海默氏病和肌萎缩性侧索硬化症）的工作模型。